Our laboratory has previously demonstrated that mice with a severe and chronic inflammatory granuloma, precipitated by pristane treatment, provide an excellent model for studies on the development of acute myeloid leukemia. Injection of such mice with retroviruses can result in myeloid leukemias that resemble AML in man. Studies on the preleukemic events leading up to the development of one of these types of leukemias, called M-ML or MF-ML, has been a recent focus. These promonocytic leukemias are caused by injection of Moloney murine leukemia virus (M-MuLV) or MF-MuLV in adult pristane-treated BALB/c mice and have been shown to be transformed at least in part by insertional mutagenesis of the c-myb gene. Evidence now indicates that, although transformed cells appear in the peritoneal cavity during the acute stage of disease, leukemia induction can involve the spleen in early stages. In addition, Pristane may facilitate preleukemic events in hematopoietic organs, since, in response to pristane, the spleens and livers show increased levels of progenitor cells committed to the granulocyte/macrophage lineage and the bone marrows have an increased rate of multipotential stem cell turnover. Results also suggest that prostaglandin E2 (PGE2) produced during the developmental stages of the leukemia may facilitate the induction of leukemia by virus. PGE2 is produced by the leukemic cells and PGE2 can abrogate the inhibitory effects of indomethacin on leukemia development. Other models of acute myeloid leukemia are being developed in the laboratory and a recent murine protocol involves inoculation of amphotropic MuLV (4070) into pristane-treated DBA/2 mice. Data suggest that novel genetic mechanisms involving the c-myb gene may be implicated in the transformation of some of these tumors, since these leukemias produce small aberrant c-myb proteins, but their c-myb genetic locus shows no overt signs of DNA rearrangement or viral insertion.